BioCryst at Barclays Conference: Strategic Growth and Pipeline Focus

On Tuesday, 11 March 2025, BioCryst Pharmaceuticals (NASDAQ: BCRX) presented at the Barclays 27th Annual Global Healthcare Conference. The company outlined its financial performance and strategic focus, highlighting both achievements and challenges. While BioCryst is nearing profitability, it aims to balance the growth of its flagship product Orladeyo with advancements in its pipeline.

Key Takeaways

• BioCryst expects Orladeyo to achieve peak global sales of $1 billion.
• The company is on track for EPS profitability by the end of this year.
• Pipeline developments include BCX-7725 for Netherton syndrome and a novel delivery method for evarestat in DME.
• BioCryst is confident in Orladeyo’s market position despite upcoming competition.

Financial Results

• Revenue Guidance: Orladeyo is projected to generate $535 million to $550 million in 2024.
• Profitability: BioCryst achieved an operating profit last year and expects EPS profitability by year-end, with full-year EPS profitability next year.
• U.S. Peak Sales Target: The company aims for $800 million in peak sales for Orladeyo, relying on adding 200 new patients annually and increasing the paid rate to 85%.

Operational Updates

• Orladeyo Performance: The oral treatment for hereditary angioedema (HAE) has demonstrated over 90% reduction in attack control, supported by real-world evidence.
• Competitive Landscape: Despite new entrants like FORVARIS and ORADRA, BioCryst emphasizes Orladeyo’s efficacy and convenience as an oral treatment.

Future Outlook

• Pipeline Progress: BCX-7725 is in Phase 1 for Netherton syndrome, targeting KLK5 inhibition. Data on skin healing is expected by year-end.
• DME Program: Evarestat is being tested for diabetic macular edema using a novel suprachoroidal delivery method, with promising preclinical results.

Q&A Highlights

• Netherton Syndrome: The Phase 1 study design focuses on safety and efficacy in skin healing, with data collection on skin mark levels.
• DME Program: The clinical trial assesses changes in edema and visual acuity following a single dose of evarestat.
• Orladeyo Sales Confidence: BioCryst’s strategy includes patient growth and small price increases, supported by strong real-world evidence.

For a detailed account, refer to the full transcript below.

Full transcript - Barclays 27th Annual Global Healthcare Conference:

Gina Wen, SMICC Biotech Analyst, Barclays: Thank you. Good morning, everyone. My name is Gina Wen.

I’m SMICC Biotech Analyst at Barclays. It is my great pleasure to have our next presenting company, Boucrest Pharmaceuticals on stage. On stage with me, we have John Booth, Chief Communication Officer. We also have Helen Fekry, Chief Research and Development Officer. Giving Helen here, we will discuss a lot about the pipeline assets and then we’ll dive into the science and preclinical data and the clinical development.

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: Thanks for having us very much. And Helen and I will both be making some forward looking statements. So please review those forward looking statements in our SEC filings.

Gina Wen, SMICC Biotech Analyst, Barclays: Good. So before I dive in, ask Helen a lot of the questions, I wanted to ask John first regarding the recent I mean, if you wanted to give a quick overview, and then we can dive into the questions or we can start. Yes.

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: So just at a high level, for those of you who don’t know BioCryst well, we are a company focused on developing medicines for rare diseases. Our lead product is a commercial program, Oralideo, for hereditary angioedema. It’s the first oral treatment to prevent attacks of hereditary angioedema. It’s been on the market for five years now and our guidance this year is $535,000,000 to $550,000,000 in revenue, expecting peak sales of $1,000,000,000 So we’ve got a thriving commercial product in Orlodeo. We’ve got an exciting pipeline, which I know we’ll talk a lot about today.

We’ve got by the end of the year, we’ll have two programs in the clinic and our first data coming from those programs. And then from a financial perspective, the company is right on the cusp of profitability. We achieved an operating profit last year and expect by the end of this year, we’ll be EPS profitable and on a full year basis, EPS profitable next year and that profitability really starts to expand over the coming years. So the company is in a fantastic position financially, commercially and from an R and D point of view.

Gina Wen, SMICC Biotech Analyst, Barclays: Great. Since you brought up the financial goal of reaching profitability, so you do have a pipeline assets pretty active compared to the maybe past. We have two could be potentially very interesting, exciting assets there. So how do you regarding the strategy, how do you balance these two out regarding maintaining

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: profitability? So I’ll answer that. So we think we can do both. Orlodeo has put us in a great position with strong performance. We’re on a path to profitability next year, full year EPS positive for the year.

And that is together with bringing forward our pipeline. So we intend to be continuing to do that. We have two molecules in the clinic, as John mentioned, both with data expected this year. And so, that’s included. And so, we expect to be doing both move to profitability and bringing pipeline forward so that we can bring a second product forward.

Our goal is to have a second commercially successful product after Oladao.

Gina Wen, SMICC Biotech Analyst, Barclays: Great. Okay. I will start with the Melitin syndrome, the BCX-seventeen thousand seven hundred and twenty five. So maybe first, can you lay out the scientific rationale targeting the KLK5? So we understand the some parts the mutation regarding the SPIN5 genes?

And then maybe walk

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: us through like why you’re picking this target and what kind of a preclinical data to support this approach? Sure. So we’re targeting treatment for Nethersen syndrome, which is an ultra rare genetic disease. It’s one for which there’s no disease modifying therapy available. And as a genetic disease, it has a it’s known to have a mutation that leads to abnormal protein function and therefore KLK5 overactivity or unregulated activity.

Our goal is to replace the missing protein function. So we’re developing a KLK5 inhibitor. It’s potent and very has potency, specificity and high affinity. And our goal with that is to improve, as I said, the disease by replacing the missing functional protein. KLK5 as a target is important in this disease because that is the driver of all of the downstream effects of the disease.

It’s the driver of dysfunctional keratinization of the skin and early separation of the skin, which leads to a poor skin barrier and poor skin function to a very severe degree. It’s also a driver of inflammation in the skin and a cascade of cytokines downstream from KLK5 as well. So there’s both the KLK cascade, which improves and affects skin and cytokines, which affects inflammation in an atopic like picture to the disease. So, our approach is to deliver KLK5 inhibition to replace that normal inhibition and to do it with a therapy then that is delivered as a subcutaneous therapy. So it’s very potent.

So small volume necessary to give the effect and to do so in a way that we expect to be able to look at and hopefully completely change patients’ skin. We’re looking for healing of the skin.

Gina Wen, SMICC Biotech Analyst, Barclays: So maybe highlight some of the preclinical data? Yes. So the preclinical data as

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: a genetic disease that has a sort of single pathway gene to protein to disease outcome, It means that the preclinical data is actually fairly simple. There are models preclinically that show what happens when you don’t have the gene and that show what happened then when you correct with KLK5 activity. So, there’s a model that shows a knockout mouse model that shows missing of the gene and you see the disease. Then there’s even further knockout KLK5, which demonstrates control of KLK5 and you see return to normal. So that is the most important preclinical data, because it tells us that if we can correct for that gene mutation and the missing protein function, we can correct for the disease.

Gina Wen, SMICC Biotech Analyst, Barclays: And so you mentioned the knockout mice. What other preclinical animal model you tested? And then how would that help you translate to the, say, the Phase one understanding regarding the dosing and the dosing frequency?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So that knockout model, as I said, is the most important model for this disease. What we’ve then done is looked at 17725 and assessed this BCX 17,725 assessed potency for KLK5 inhibition, specificity and affinity for KLK5 inhibition. So, we’ve assessed that also preclinically, and we’ve demonstrated that it has very high potency. It also has very high affinity, which is important because that means sticking to the target and staying on the target. So, what we’ve been able to show is that it stays on the target.

And what we expect then is, as it translates through to humans, we’ll be looking for one dose and the effect of one dose over time as that target that KLK5 molecule rises through the skin and then is that layer of skin is shed.

Gina Wen, SMICC Biotech Analyst, Barclays: So when you say high specificity, can you give quantified numbers regarding the target tissue versus or like target versus others, the selectivity wise?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So what we’re going to focus back on KLK5. We really are looking for KLK5 activity. And so, we’re looking for and we’ll be looking for this in patients this year. We’re looking for activity in KLK5 as a marker that the drug is actually getting to the skin and having the effect in the skin. And then ultimately, we’ll be looking for the clinical outcome, which is healing of the skin.

Gina Wen, SMICC Biotech Analyst, Barclays: What’s the half life of the drug?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So the half life, at the moment we have preclinical data and we’re in a healthy volunteer study, so we’re gathering data in humans as well. We anticipate the half life to be such that we could dose about every two weeks in the clinic.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. So maybe help us understand regarding the Phase I data, I’ll say the selecting of the dose and the dosing frequency and based on what data and why you’re choosing certain dose range and do you expect to already having the within the therapeutic window even with the first dose?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: Yes. So, this is an interesting program because we can assess first in healthy volunteers to get through some of the basic questions you have to ask is first in human, some safety, the pharmacokinetics and the plasma exposure. But it’s a disease where the missing function and what we’re looking for biomarkers is not present in healthy volunteers. So, in our Phase one study, we’ll be including patients immediately early on, and that will be this year dosing in patients. And we’ll be looking for the activity in the skin in this Phase one study.

We’re looking for this year, I’m going to give you a couple of things that we’re looking for. Safety and pharmacokinetics, which then leads us the ability to dose in patients and to know that we’re dosing in about the right range for the effect that we want in patients. That means that this year we’ll be then looking in patients with that range of dosing for the penetration in the skin, the activity on target in the skin, but and then ultimately that clinical healing. And we think we’ll get to the clinical outcome this year.

Gina Wen, SMICC Biotech Analyst, Barclays: So then from healthy volunteer, what are you looking for? You mentioned CTPD and that will help you determine the dosing frequency. What about the dose also the exposure?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: We’re really just looking for confirmation of what we saw pre clinically and then we see confirmation of what we saw pre clinically in terms of the level exposure and ability to dose perhaps every two weeks, then we’ll be moving straight to patients. And I want to emphasize this as well. So moving to patients is really important because that’s where we’ll have the opportunity to confirm that the drug is having the effect, but also to confirm in this disease when you have that effect in the skin, you then see healing of the skin.

Gina Wen, SMICC Biotech Analyst, Barclays: So, for the patient data, because kiloK5 will up regulate and you try to knock down right reduce the K5 expression. So for the healthy volunteer because they are normal level, will you still be able to see some level of reduction or you try not to touch too much on that part?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So we don’t expect to see the changes that we’d be looking for in patients. We don’t expect to see that in healthy volunteers. And KLK5 activity is normal in healthy volunteers, and it’s not actively binding in the layers of the skin that we’re targeting. So, we would not expect to see either drugs sticking in the skin or drug having an activity on KLK5 in the skin. And that’s part of the reason why it’s so important then to have patients early in the study is because we’ve had the basic confirmation of our expectation for dose ranges and timing of the interval of dosing and move straight to patients so that we can get to this assessment sort of understanding is the drug having the effect that we want and seeing it potentially very few patients.

We do expect this year to have a handful of patients in the study with data after several exposures with the drug, several sort of doses over an interval. And it doesn’t take very many patients to be able to see an effect. This is one of the benefits of a genetic disease where gene protein disease outcome is that we could in our first patient even see improvement in the skin and that will be very exciting to us.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. Would that be classic three plus three study design for the patient? And what kind of data we will be looking for? We would need to collect the biopsy and to look at the KLK5 level and try to see about the like what kind of data you will share with us, biomarker data and also the skin killing data?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So, this will be a simple dosing study, not necessarily a three plus three design. A three plus three design is typically to look for safety signals and that doesn’t apply here. But we’ll be looking for dosing the first few patients. We’ll be looking at the skin, the bioassay of skin mark levels as I said. But then we’re also looking for changes in the skin measured by things like the validated scales that are used for atopic dermatitis like the IGA or investigator assigned their score of skin healing.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. When you say dosing interval, were you using like one dose and a different frequency or you will explore different doses?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So, we really just need to know what happens in the first few patients to then confirm what the dosing frequency would be for a pivotal study. So we’ll start with maybe once a week, maybe once every two weeks. But the outcome from those first few patients is do we get the exposure in the skin. And I know I’m sort of emphasizing this, but it really is important and it’s very easy to see in those first few patients.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. And that dose selection is mainly based on the healthy volunteer. So you think that dose, whatever you select should be efficacious. And that the differences you are doing in Phase one, you’re just different frequency of dosing. Is my understanding correct?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So we will start with one dose level in patients. If we don’t see effect in the skin, we’ll dose range from there. So if we don’t see effect in the skin, we go up. If we have hit it and we see effect in the skin, then we’ll just proceed forward.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. And that when you say hit it, you are looking at it.

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: Healing in the skin. Healing in the skin.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. And how soon do you think that we should see that, the skin healing?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: Skin turnover is pretty fast in the other hand syndrome. We’ll be looking for outcomes within a matter of weeks, and then four week outcomes, eight week outcomes, twelve week outcomes. So, we would expect to be looking pretty quickly, and we would expect and we’re looking for a very large and dramatic effect. So we’re looking for one that is easily visible, easily detectable and has a substantial change on that physician score.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. Very helpful. So 2025 data update maybe lay out under what how much data package you have? Do you think it’s ready to share with the investors? And then realistically, how what which part of the 2025 you will be able to share that data?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So towards the end of the year, we’ll probably bundle it all together because the meaningful outcomes are going to be that skin healing in patients. So we’ll just combine everything that we know and have something later this year. But it’s likely to be one update not sort of incremental information because what matters is that patient data.

Gina Wen, SMICC Biotech Analyst, Barclays: So when you share that update, will you be able to also have some initial FDA feedback to share with the investor regarding the next step, say pivotal study or the path to approval?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So I don’t expect that we’ll have pivotal study plans to announce by the end of the year. I expect that we’ll have information sort of confirming and confirming that the drug is effective and that there’s clinical outcomes and that preparing to move into the next step, which we put pivotal trials. We’ll, of course, need to be interacting with regulators along the way because in order to start a trial, we have to have some regulatory interactions. And you could expect that we’ll be having typical interactions both for getting studies started and for sort of long term planning for the program.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay, great. Now switch gear to your DME program. So maybe a little bit background, why selecting evarestat? And then maybe first, why this TARKI, CaliClean target is a good target? And then second, and you do have, we saw this failed in the HAE development in the past, you discontinue.

So why selecting this asset for DME?

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: Yes, sure. So this is we think this is the right drug for this space. And in fact, we learned a lot in that HAE program. The reasons for vorlistat not being successful in HAE were related to poor exposure because it’s poorly soluble. So, as an oral drug, it was not the ideal drug.

And we moved on to Orlodeo, which has been a much better drug and is showing that in the market. But if rolstat is as poorly soluble, it is actually ideal to put it in a suspension in a closed space and let it slowly dissolve over time. So, it’s got ideal physical characteristics for instilling in a space and then we’re going to plan to put in suprachoroidal space or bathing the outside of the eye, bathing near the retina. And that means that as a suspension, it will slowly dissolve, it will slowly deliver, and it will have sustained exposure over a long period of time. We have some animal data to show that the levels in the retina after one dose are sustained well above the effective target out to one hundred and eighty days.

So that suggests that this is something that in the clinic could be dosed perhaps once or twice a year. And that would be a really important change for patients with DME where VEGF inhibitors typically are dosed every month. In terms of plasma catalactrine, and this is a mechanism of action, so what we know in diabetic macular edema is that VEGF inhibitors have really changed the field. What we also know is that somewhere around forty percent of patients are not well served by VEGF inhibitors. So there’s clearly something else going on as a mechanism of diabetic macular edema.

We know from data that has been published that in the eye of patients with DME, there is detectable VEGF and some patients who don’t have detectable VEGF. And in those, there is detectable plasma catalactrine. So that suggests that it could be an alternative target, an alternative mechanism for diabetic macular edema. Plasma catalactrine is involved in contact activation and in vascular leakage. And our more recent data, preclinical data that we showed earlier this year, is actually very helpful in confirming that that vascular leakage can be influenced and specifically changed with plasmacalicline.

So we had an animal model, looked at the rabbit, we looked at suprachoroidal dosing, so using avorostatin the same way, in the same location that we would use in the clinic. And in a model that’s well established for assessing VEGF inhibitors, assessing whether they can produce leakage in the retinal vascular in the eye, we were able to show that using a voristat plasma kalochrine inhibition only, no VEGF inhibitors, we saw reduction in leakage to a very similar extent. So that confirms

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: for

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: us the plasma calacrine inhibition is by itself able to reduce retinal vascular leakage in the eye. And so between those two pieces of data, we now have the confidence to go into the clinic and move straight to patients and be able to dose in patients. And we think with one dose, we could assess over a month, two months, three months and look for clinical outcomes with that dose. What we’ll be looking for I’ll say a little bit more. What we’ll be looking for is change in edema.

And this is a known marker in this disease. It’s known to be predictive of changes in visual acuity. It’s used as

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: a

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: sort of an interim way of assessing likelihood of success in the drug. And so, with our first patients enrolled with their first dose of Evorostat, we’ll be following those patients without needing to dose other doses to be able to see then at one month, two months, three months, are we seeing a change in that level of edema in the eye? And then over a longer period of time, are we seeing changes in visual acuity? So, we have a unique opportunity to with one dose study assess outcomes in the eye as well.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay, good. We only have a few minutes. I do wanted to ask about the Oladeo. John, you did mention the $800,000,000 revenue guidance, right, in 2029. Maybe can highlight what are the key assumptions there and then why you feel so confident that despite the upcoming multiple potential competitor entrants, you still feel confident that guidance could be achievable.

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: Yes. I’ll walk you through the components of $800,000,000 and Helen can share a little bit on the confidence that we’ve got. So to get to $800,000,000 in peak sales in The U. S, we need to add about 200 net new patients on an annual basis. We did that last year and again in two years ago, we’re well on our pace with very strong demand for Orlodeo.

Most of those patients are switching from other prophylactic or acute therapies. We also need to continue to increase the rate of patients who are paying for LIDEO versus getting free drugs. So, to get to $800,000,000 we need a paid rate of eighty five percent and we made additional progress last year getting the number at the end of the year up seventy three point five percent and we see the path to eighty five percent getting clearer and clearer as we make more and more progress there. We think we’ll end this year around eighty percent paid. And then finally, there’s a small component of price increase associated with that assumption.

We’ve taken 5% price increases over the last couple of years. So that’s how we get to $800,000,000 in the trajectory we’re on with the guidance increase that we just announced at the last quarter. We’re extremely confident in achieving $800,000,000 in PQS sales and $1,000,000,000 in global sales. And Helen can talk to you about some of the reasons for that confidence.

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: Yes. So, I’m going to talk a little bit about some of what’s data that we just brought out at Quad AI, or is that AAAAI, in San Diego just recently. And we had some of our largest real world data sets there in two different abstracts presented at AAAAI. What’s remarkable is we have data now on over 800 patients who’ve been on Orlodeo. We it was presented in two abstracts looking at the type one and two HAE as well as C1 normal HAE.

And we see tremendous efficacy. We see it’s for patients who do well in Orla Deo, they do very well. And that’s now reproduced in real world evidence with longer term follow-up in large numbers of patients. That gives us confidence that patients who are on Orla Deo, we’re doing well on Orla deo, they are continuing to do very well and we’re seeing that in such large numbers that it’s really hard to argue with.

Gina Wen, SMICC Biotech Analyst, Barclays: And maybe any thoughts on the potential competitors, for example, FIFARIS, ORADRA, I know they are still a bit behind, any concern there? And of course, there are other subcu less frequent dosing, those also could potentially later will enter the market.

Helen Fekry, Chief Research and Development Officer, Boucrest Pharmaceuticals: So maybe I can speak to sort of FORVARIS and you can talk about the others. So FORVERIS, so there’s we think oral clearly is differentiated for treatment for HIE. Very pleased with how ORILDEA has been doing as a result. ORILDEA was in the fifth year on the market. And by the time another oral will be available, it will have been on the market for eight years.

So this is an opportunity for us to continue to build the real world evidence data set to continue to get patients on drug and doing well. And we think that’s in a sticky market. It’s going to be harder than for anyone else with another oral to come in and have patients do well.

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: Yes. And I think in terms of the injectables that are coming onto the market for patients who are doing well on Orlodeo and doing well on Orlodeo is 90 plus percent reduction in attack control and the real world evidence that Helen was describing. So many, many attack free patients or very few attacks. Those patients who are getting that kind of result with an oral capsule once a day, the injectables we don’t think are going to offer anything incremental that’s going to motivate an oral Lidale patient who’s well controlled to switch. And we actually think that the discussions that are going to happen between physicians and patients as new entrants come into the market are going to be discussions about the options, the new options and do you want to switch.

And we’re going to be right there for those discussions with the relationships we’ve built over the five plus years of launch. And we think there’s an opportunity for them to consider if they’re not on Orla DAO, but they’re open to a switch, so trying the oral medicine first. So, we’re looking forward to continued growth as these new entrants come on board.

Gina Wen, SMICC Biotech Analyst, Barclays: Great. We’re on time. Thank you very much, Helen and John. And we look forward to the data update later this year. Thank you, Jim.

John Booth, Chief Communication Officer, Boucrest Pharmaceuticals: Thanks, Tina.

Gina Wen, SMICC Biotech Analyst, Barclays: Okay. Thank you. Thank you, everyone.

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